Synaptic Vesicle2A (SV2A) Positron Emission Tomography(PET) Imaging as a Marker of Therapeutic Response in a Mouse Modelof Depression

In this preclinical pilot study, we used [¹¹C]­UCB-J PET imaging to monitor the synaptic modulation in depression and after fluoxetine. PET imaging was performed in a validated mouse model of depression/anxiety (CORT model), and the effect of 5-week treatment with fluoxetine was tested. Depression/anxiety phenotype and antidepressant action of fluoxetine were confirmed using the novelty-suppressed feeding test, previously validated in the CORT model. PET data showed significant decreases of volume of distribution (<i>V</i>_T) of [¹¹C]­UCB-J in most brain regions of CORT mice compared with controls. After 5 weeks of fluoxetine, a trend toward restoration of <i>V</i>_T values to control levels was observed, although it reached significance only in the olfactory bulb. These preliminary data support the use of [¹¹C]­UCB-J PET imaging and the CORT model to study the synaptic modulation of antidepressants. It provides excellent translational opportunities to study the relationship between synaptic plasticity and the clinical efficacy of antidepressants.